Schinus terebinthifolius Raddi is a South American plant with medicinal properties. We report the extraction of compounds from S. terebinthifolius fruits using supercritical CO2 (scCO2), with emphasis on the effects of scCO2 pressure (100–300 bar) and temperature (40–60 °C) on global yield, volatile compounds, and antiproliferative activity against nine human tumor cell lines. Supercritical extracts obtained at 50–60 °C, independently of pressure, showed potent activity against kidney cancer with total growth inhibition <3.9 μg/mL. Furthermore, extracts obtained at 200 bar and 50 °C showed potent activity against multidrug-resistant ovarian, prostate, and ovarian tumor cell lines, and glioma. Gas chromatography-mass spectrometry revealed the following volatile compounds: δ-3-carene, α-phellandrene, limonene, germacrene D, and caryophyllene. The results suggest that sesquiterpenes may be the metabolites responsible for the antiproliferative activity. However, future work involving fractionation of the extracts might shed light on the chemical compounds responsible for each antiproliferative activity Ver menos